Annals of Surgical Oncology

, Volume 22, Issue 4, pp 1324–1331 | Cite as

Aggressive Therapeutic Strategies Improve the Survival of Hepatocellular Carcinoma Patients with Performance Status 1 or 2: A Propensity Score Analysis

  • Chia-Yang Hsu
  • Po-Hong Liu
  • Yun-Hsuan Lee
  • Cheng-Yuan Hsia
  • Yi-Hsiang Huang
  • Yi-You Chiou
  • Ya-Ju Tsai
  • Teddy S. Nagaria
  • Teh-Ia Huo
Hepatobiliary Tumors



Targeted therapy or chemotherapy is suggested as standard treatment for hepatocellular carcinoma (HCC) patients with performance status (PS) 1–2 according to the Barcelona Clinic Liver Cancer (BCLC) system. The underlying rationales have not been fully studied.


This study enrolled 2,620 HCC patients. One-to-one matched pairs between HCC patients receiving aggressive anti-HCC treatments (resection, transplantation, ablation, and transarterial chemoembolization) and those receiving targeted therapy or chemotherapy or best supportive care were generated by using the propensity score with a matching model. Survival analysis was performed with the Kaplan–Meier method and the log-rank test. Mortality risk was calculated with the Cox proportional hazards model.


Of 793 patients with PS 1–2, 64 % received aggressive anti-HCC treatments against the suggestion of the BCLC system. The patients receiving aggressive anti-HCC treatments had significantly milder cirrhosis, a smaller tumor burden, and better long-term survival than the patients undergoing targeted therapy or chemotherapy or best supportive care (all p < 0.05). With the use of propensity scores, 166 pairs of matched HCC patients with PS 1–2 were selected from different treatment groups. After matching, patients were comparable in age, gender, severity of cirrhosis, tumor burden, and prevalence of diabetes mellitus (all p > 0.05) at baseline. In the propensity score model, patients with PS 1–2 undergoing aggressive anti-HCC treatments had significantly better long-term survival (p < 0.0001). The adjusted hazard ratio of the choice for targeted therapy or chemotherapy or best supportive care to the choice for aggressive anti-HCC treatments was 2.028 (p < 0.0001).


According to the findings, HCC patients with PS 1–2 should consider aggressive anticancer treatments if no contraindication is noted. Adjustment of the BCLC treatment allocation is needed to enhance its prognostic accuracy.


Sorafenib Propensity Score Tace Supportive Care Barcelona Clinic Liver Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was supported by Grants from the Center of Excellence for Cancer Research at Taipei Veterans General Hospital (DOH102-TD-C-111-007) in Taiwan, from the Taipei Veterans General Hospital (V103C-008) in Taipei, Taiwan, and from the Ministry of Education, Aiming for the Top University Plan (103AC-P618) in Taiwan.



Supplementary material

10434_2014_4151_MOESM1_ESM.doc (39 kb)
Supplementary material 1 (DOC 39 kb)


  1. 1.
    Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134:1752–63.CrossRefPubMedGoogle Scholar
  3. 3.
    Dufour JF, Bargellini I, De Maria N, et al. Intermediate hepatocellular carcinoma: current treatments and future perspectives. Ann Oncol. 2013;24(Suppl 2):ii24–9.Google Scholar
  4. 4.
    Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2.CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.Google Scholar
  6. 6.
    Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19:329–38.CrossRefPubMedGoogle Scholar
  7. 7.
    Hsu CY, Lee YH, Liu PH, et al. Decrypting cryptogenic hepatocellular carcinoma: clinical manifestations, prognostic factors and long-term survival by propensity score model. PLoS One. 2014;9:e89373.Google Scholar
  8. 8.
    Hsu CY, Hsia CY, Huang YH, et al. Comparison of surgical resection and transarterial chemoembolization for hepatocellular carcinoma beyong the Milan criteria: a propensity score analysis. Ann Surg Oncol. 2012;19:842–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001;35:421–30.CrossRefPubMedGoogle Scholar
  10. 10.
    Lee YH, Hsu CY, Hsia CY, et al. Alcoholism worsens the survival of patients with hepatitis B virus and C virus-related hepatocellular carcinoma. Hepatol Int. 2013;7:645–54.CrossRefGoogle Scholar
  11. 11.
    Hsu CY, Lee YH, Huang YH, et al. Ascites in patients with hepatocellular carcinoma: prevalence, associated factors, prognostic impact, and staging strategy. Hepatol Int. 2013;7:188–98.CrossRefGoogle Scholar
  12. 12.
    Hsu CY, Lee YH, Hsia CY, et al. Performance status in patients with hepatocellular carcinoma: determinants, prognostic impact, and ability to improve the Barcelona Clinic Liver Cancer system. Hepatology. 2013;57:112–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Hsu CY, Huang YH, Hsia CY, et al. A new prognostic model for hepatocellular carcinoma based on total tumor volume: the Taipei Integrated Scoring system. J Hepatol. 2010;53:108–17.CrossRefPubMedGoogle Scholar
  14. 14.
    Austin PC, Schuster T. The performance of different propensity score methods for estimating absolute effects of treatments on survival outcomes: a simulation study. Stat Methods Med Res. 2014 (in press).Google Scholar
  15. 15.
    Austin PC. A comparison of 12 algorithms for matching on the propensity score. Stat Med. 2014;33:1057–69.CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Hsu CY, Lee YH, Hsia CY, et al. Performance status enhances the selection of treatment for patients with hepatocellular carcinoma within the milan criteria. Ann Surg Oncol. 2013;20:2035–42.CrossRefPubMedGoogle Scholar
  17. 17.
    Lee YH, Hsia CY, Hsu CY, et al. Total tumor volume is a better marker of tumor burden in hepatocellular carcinoma defined by the Milan criteria. World J Surg. 2013;37:1348–55.CrossRefPubMedGoogle Scholar
  18. 18.
    Lee YH, Hsu CY, Huo TI. Assessing liver dysfunction in cirrhosis: role of the model for end-stage liver disease and its derived systems. J Chin Med Assoc. 2013;76:419–24.CrossRefPubMedGoogle Scholar
  19. 19.
    Gomaa AI, Hashim MS, Waked I. Comparing staging systems for predicting prognosis and survival in patients with hepatocellular carcinoma in egypt. PLoS One. 2014;9:e90929.CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Kim BK, Kim SU, Park JY, et al. Applicability of BCLC stage for prognostic stratification in comparison with other staging systems: single-centre experience from long-term clinical outcomes of 1,717 treatment-naive patients with hepatocellular carcinoma. Liver Int. 2012;32:1120–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Kim BH, Park JW, Nam BH, et al. Validation of a model to estimate survival in ambulatory patients with hepatocellular carcinoma: a single-centre cohort study. Liver Int. 2014 (in press).Google Scholar
  22. 22.
    Weinmann A, Koch S, Niederle IM, et al. Trends in epidemiology, treatment, and survival of hepatocellular carcinoma patients between 1998 and 2009: an analysis of 1,066 cases of a German HCC Registry. J Clin Gastroenterol. 2014;48:279–89.CrossRefPubMedGoogle Scholar
  23. 23.
    Ruzzenente A, Capra F, Pachera S, et al. Is liver resection justified in advanced hepatocellular carcinoma? Results of an observational study in 464 patients. J Gastrointest Surg. 2009;13:1313–20.CrossRefPubMedGoogle Scholar
  24. 24.
    Kudo M, Osaki Y, Matsunaga T, et al. Hepatocellular carcinoma in Child-Pugh C cirrhosis: prognostic factors and survival benefit of nontransplant treatments. Dig Dis. 2013;31:490–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Yau T, Tang VY, Yao TJ, et al. Development of Hong Kong Liver cancer staging system with treatment stratification for patients with Hepatocellular Carcinoma. Gastroenterology. 2014 (in press).Google Scholar
  26. 26.
    Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.CrossRefPubMedGoogle Scholar
  27. 27.
    Tokushige K, Hashimoto E, Yatsuji S, et al. Prospective study of hepatocellular carcinoma in nonalcoholic steatohepatitis in comparison with hepatocellular carcinoma caused by chronic hepatitis C. J Gastroenterol. 2010;45:960–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Cabibbo G, Genco C, Di Marco V, et al. Predicting survival in patients with hepatocellular carcinoma treated by transarterial chemoembolisation. Aliment Pharmacol Ther. 2011;34:196–204.CrossRefPubMedGoogle Scholar
  29. 29.
    Liu PH, Lee YH, Hsia CY, et al. Surgical resection versus transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombosis: a propensity score analysis. Ann Surg Oncol. 2014;21:1825–33.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Chia-Yang Hsu
    • 1
    • 4
  • Po-Hong Liu
    • 1
    • 4
  • Yun-Hsuan Lee
    • 1
    • 7
  • Cheng-Yuan Hsia
    • 1
    • 5
  • Yi-Hsiang Huang
    • 2
    • 4
  • Yi-You Chiou
    • 1
    • 6
  • Ya-Ju Tsai
    • 8
  • Teddy S. Nagaria
    • 9
  • Teh-Ia Huo
    • 1
    • 3
    • 4
  1. 1.Faculty of MedicineNational Yang-Ming University School of MedicineTaipeiTaiwan
  2. 2.Institute of Clinical MedicineNational Yang-Ming University School of MedicineTaipeiTaiwan
  3. 3.Institute of PharmacologyNational Yang-Ming University School of MedicineTaipeiTaiwan
  4. 4.Division of Gastroenterology, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
  5. 5.Department of SurgeryTaipei Veterans General HospitalTaipeiTaiwan
  6. 6.Department of RadiologyTaipei Veterans General HospitalTaipeiTaiwan
  7. 7.Department of MedicineYuanshan Branch of Taipei Veterans General HospitalI-LanTaiwan
  8. 8.Queen of Angels HospiceArcadiaUSA
  9. 9.Department of PathologyUniversity of TorontoTorontoCanada

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